High Resolution Mapping of Foveal Ganglion Cell Receptive Fields in the Living Primate Eye

活体灵长类动物眼睛中心凹神经节细胞感受野的高分辨率绘图

• 批准号: 10534734
• 负责人: DAVID R WILLIAMS
• 金额: $ 55.48万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534734
• 关键词: Acceleration; Anatomy; Brain; Calcium; Calcium Signaling; Cells; Classification; Code; Color; Color Visions; Complement; Complex; Cone; Dedications; Development; Disease; Electrophysiology (science); Eye; Floods; Fluorescence; Funding; Grain; Histologic; Histology; Human; Image; Imaging Techniques; In Vitro; Individual; Injury; Investigation; Knowledge; Laboratories; Light; Location; Maps; Mediating; Methods; Monkeys; Morphology; Mus; Noise; Ophthalmoscopes; Optical Instrument; Performance; Peripheral; Photoreceptors; Physiological; Physiology; Primates; Property; Resolution; Retina; Retinal Cone; Retinal Ganglion Cells; Scanning; Signal Transduction; Stimulus; Structure; Surveys; System; Techniques; Time; Vision; Yin; adaptive optics; arm; blind; calcium indicator; design; flexibility; fluorescence imaging; fovea centralis; ganglion cell; improved; in vivo; instrument; melanopsin; new technology; novel; novel strategies; receptive field; reconstruction; response; retinal imaging; sight restoration; spatial vision; spatiotemporal; visual stimulus

The importance for vision of the tiny fovea has been established by centuries of investigation as well as observations of the devastating consequences of its damage through injury or disease. Though evidence suggests that the fovea contains the full complement of the two dozen or so classes of ganglion cells found in peripheral retina, we know little about the physiology of these foveal cells. This gap in our understanding is the result of challenges in obtaining electrophysiological recordings from this delicate and topographically-complex structure. These challenges have been overcome by a method developed in our laboratory that allows simultaneous calcium imaging of the fluorescence responses of hundreds of foveal retinal ganglion cells in response to visual stimuli. Because this technique allows recording from single cells without damage in the living eye, we can study the same cells for months or even years, offering the opportunity to characterize the performance of each cell more thoroughly than has been possible with any prior method. Since the first submission of the proposal, we have made significant improvements in the expression of calcium indicator, GCamMP6s, in ganglion cells that increases the extent of expression to greater eccentricities, the fluorescence signal from each cell, as well as reducing the loss of ganglion cells over time. Moreover, we have designed a new ophthalmoscope with two independent adaptive optics systems, one dedicated to high resolution stimulus delivery and a second dedicated to high resolution ganglion cell recording. We have also developed an extensive battery of visual stimuli to characterize the responses of each cell in space, time, and color. This battery will include a white noise stimulus capable of identifying the locations and classes of single cone inputs to the receptive fields of foveal ganglion cells. To assist in cell classification, these physiological observations will be supplemented with ex vivo and in vivo histological analysis of the morphology of ganglion cell dendritic arbors. Armed with these improvements, we will undertake a comprehensive survey of both the physiology and anatomy of the foveal ganglion cell classes that mediate primate foveal vision.

几个世纪的调查以及 观察其通过伤害或疾病造成破坏的毁灭性后果。虽然证据 表明该中央凹包含二十种左右的神经节细胞的完整补充 周围视网膜，我们对这些凹入细胞的生理学知之甚少。我们理解的差距是 从这个精致和地形复杂的挑战获得了电生理记录的挑战的结果 结构。我们的实验室中开发的一种方法已经克服了这些挑战 同时对数百个中央凹视网膜神经节细胞的荧光反应的钙成像 对视觉刺激的反应。因为这项技术允许从单元中记录而没有损害的单个单元 眼，我们可以研究相同的细胞数月甚至数年，提供了表征的机会 使用任何先验方法，每个单元的性能都比可能更彻底了。自第一个 提交提案，我们在钙指标的表达中取得了重大改进， GCAMMP6，在神经节细胞中增加表达程度到更大的偏心率，荧光 来自每个细胞的信号，以及随着时间的流逝减少神经节细胞的丧失。而且，我们设计了 新的眼镜镜具有两个独立的自适应光学系统，一种用于高分辨率刺激 输送和第二次专用于高分辨率神经节电池记录。我们还开发了广泛的 视觉刺激的电池以表征每个单元格在时空，时间和颜色中的响应。这个电池将 包括一个能够识别单锥输入的位置和类别的白噪声刺激 凹起神经节细胞的接受场。为了协助细胞分类，这些生理观察将是 补充了神经节细胞树突状乔木的形态的体内和体内组织学分析。 通过这些改进，我们将对生理学和解剖学进行全面调查 介导灵长类动脉垂体视觉的中央凹神经节细胞类别。